The Section on Molecular Neuroscience studies the molecular mechanisms of chemically coded ionotropic and metabotropic neurotransmission in the nervous system. The ultimate goals of the project are identifying molecular components of synaptic transmission, and how these components are regulated to allow short-term and long-term information to be encoded within postsynaptic neurons and neuroendocrine cells. In 2002-2003, we have made the following advances. 1. A novel calcium-initiated signaling pathway propagated through calcineurin and CREB and regulating neuropeptide gene expression in bovine chromaffin cells has been identified 2. Bioinformatics tools (pathFinder; the STKE PC12 cell differentiation Connections MAP, the microarray database mAdb) have been collaboratively developed or adapted for use by NIMH and extramural investigators, aiding in the design and interpretation of cell signaling experiments in PC12 and bovine chromaffin cells. 3. A PACAP knock-out mouse model has been used to demonstrate that this peptide is important in neuroprotection following ischemic injury to cerebral cortex, and microarry analysis was used to identify key PACAP-dependent genes involved in neuroprotection. 4. Regulatory elements within the first exon of the VIP gene conferring cell-specific silencer function in combination with the previously characterized tissue specifier element were identified, and cis-active sequences in the cholinergic gene locus (CGL) were identified that confer transcriptional activation within the median habenular nucleus. 5. We have identified a dopaminergic component to the human enteric nervous system using histochemical probes for the vesicular monoamine transporter VMAT2, in conjunction with previously established markers for catecholaminergic traits in vivo. In summary, the work of the SMN to identify the chemical neuroanatomy and well as the mechanisms and gene targets of cell signaling via slow transmission in the nervous system has advanced with the identification of new neuronal circuits, signaling pathways, and cis-active elements within the genes targeted by slow transmitters. The pathophysiological relevance of these new targets is beginning to be appreciated through the use of microarray technology applied to neuropeptide-specific changes in neuronal transcriptomes acccompanying neuroprotection, neuroadaptation, and neuronal development and differentiation.